Ion channels play a crucial role in cell function. In addition, a substantial number of studies suggests that cell specialisation is often based on the spatial distribution of these channels on the cell surface, for example in neural cells, muscle cells and epithelial cells.
Several types of ion channels have been reported to be arranged non-randomly in a specific pattern on the cell membrane, and this appears to have important functional implications. For example, it is known that voltage-gated Na+ channels are densely distributed and co-localized with acetyl choline receptors in the neuromuscular junction, to enable effective chemical signal transmission. Further, NMDA receptors, which play an important role in neuronal signalling, are arranged in distinct spatial patterns, and their arrangement contributes to synaptic plasticity.
The spatial distribution of ion channels has mainly been studied by microscopy-based techniques using labelling methods. However, these studies provide practically no information on the functional characteristics of ion channels.
Patch clamping is a technique that can be used to investigate ion channel characteristics. However, it does not allow precise selection of a region of interest on a cell, and provides limited information on the important question of ion channel localization.
Scanning ion conductance microscopy (SICM) is a form of scanning probe microscopy (SPM) that allows high-resolution imaging of live cell surfaces, and of small sub-micrometer structures such as dendritic processes, microvilli in epithelial cells and the surface structures of cardiac myocytes. SICM has also been used in mapping exclusively ligand-sensitive ion channels such as ATP-dependent K+ channels on cardiac myocytes, by combination with whole-cell patch-clamp recording (Korchev et al, Nat. Cell Biol. 2:616–619, 2000).
In SICM, a glass micropipette is typically used as a microscope probe, to scan the sample. WO-A-00/63736 discloses that SICM can be used effectively, e.g. to scan the surface of a live cell, by controlling the position of such a probe. This is achieved in response to the ion current.